APOMORPHINE HYDROCHLORIDE HEMIHYDRATE for Parkinson's disease

Inclusion criteria

• {"criterion_text":"- Subject is an adult, at least 25 years of age, of either sex\n- Subject lives in the Netherlands\n- Subject can read and understand Dutch\n- Subject has completed the ethics board-approved Informed Consent\n- Subject is willing, competent, and able to comply with all aspects of the protocol, including multiple occasions of not taking their PD medication during a 12-hour period, and biospecimen collection\n- Diagnosis of Parkinson’s disease (idiopathic parkinsonism) by a neurologist, according to accepted clinical criteria\n- Documented peripheral levodopa resistance\n- Serum AADC enzyme activity of >144 mU/L (in sample taken in medicated condition) AND/OR faecal abundance of levodopa-metabolizing bacteria of >90,000 fragments per million"}

Exclusion criteria

• {"criterion_text":"- Significant doubt over the correctness of the diagnosis idiopathic Parkinson’s disease\n- Pregnancy or breastfeeding\n- Allergies to any of the investigational and non-investigational medications or constituents thereof\n- Documented severe and debilitating dyskinesias on levodopa, to such an extent that levodopa treatment was terminated\n- Contraindications to levodopa/benserazide\n- Present use of, or planned initiation during the study period of, advanced therapies (AT) for Parkinson’s disease including deep brain stimulation (DBS), continuous jejunal levodopa infusion (CJLI), continuous subcutaneous (fos)levodopa infusion (CSLI), apomorphine pen injections or continuous subcutaneous apomorphine infusion (CSAI)\n- Any antibiotic therapy during the study period and in the 12 months preceding it, unless participant only participates in apomorphine substudy and is selected for inclusion based solely upon AADC activity, not bacterial abundance\n- Present, or in the past 14 days, use of non-selective monoamine oxidase (MAO) inhibitors (including tranylcypromine) or dual use of a selective MAO-B inhibitor (including rasagiline, safinamide) and a selective MAO-A inhibitor (including moclobemide)\n- Present, or in the past 4 weeks, use of any probiotic preparations, unless participant only participates in apomorphine substudy and is selected for inclusion based solely upon AADC activity, not bacterial abundance\n- Atypical or genetic parkinsonism, or parkinsonism caused by a structural laesion of the brain\n- Levodopa-resistant tremor, unless the subtotal of the ‘OFF’ MDS-UPDRS III tremor scores (item 3.15-3.18) makes up less than 15% of the ‘OFF’ MDS-UPDRS III total sum score\n- Presence of dementia\n- Current presence of hallucinations or delusions, or history of developing hallucinations or delusions under dopaminergic therapy. Exception: hallucinations or delusions not currently present AND currently adequately treated with a cholinesterase inhibitor to prevent recurrence.\n- Fear of needles/injection\n- Co-morbidities that would hamper interpretation of parkinsonian disability, such as coincident musculoskeletal abnormalities\n- Not able to stand or walk without the assistance of another person (walking aids are not an exclusion criterion)\n- Presence of gastrointestinal disease associated with impaired drug absorption (e.g. coeliac disease)"}

Primary endpoints

• {"endpoint_text":"- Proportion of responders (defined as >30.0% decrease in MDS-UPDRS-III compared to pre-treatment), apomorphine versus levodopa","definition_or_measurement_approach":"Responders defined as >30.0% decrease in MDS-UPDRS-III compared to pre-treatment; primary comparison: apomorphine versus levodopa; measured using MDS-UPDRS-III scores before and after treatment and calculating proportion meeting the >30% reduction threshold."}
• {"endpoint_text":"- MDS-UPDRS-IIIΔOFF-ONΔposttreatment-pretreatment, rifaximin compared to placebo","definition_or_measurement_approach":"Change in the OFF-ON difference of MDS-UPDRS-III post-treatment versus pre-treatment; primary comparison: rifaximin versus placebo; measured by computing MDS-UPDRS-III OFF-ON differences before and after treatment and comparing the delta between arms."}

Secondary endpoints

• {"endpoint_text":"- MDS-UPDRS IIIΔOFF-ON","definition_or_measurement_approach":"Change in MDS-UPDRS-III OFF-ON difference; measured by MDS-UPDRS-III assessments in OFF and ON states."}
• {"endpoint_text":"- Composite Clinical Motor Score (CCMS)","definition_or_measurement_approach":"Composite motor outcome measure (CCMS) as defined in protocol; measured using constituent motor assessments as per protocol."}
• {"endpoint_text":"- Modified Hoehn & Yahr scale","definition_or_measurement_approach":"Staging on the Modified Hoehn & Yahr scale; measured by clinician-rated scale assessments."}
• {"endpoint_text":"- Global Rating of Change (GRC)","definition_or_measurement_approach":"Participant or clinician global rating of change; measured using the GRC instrument as specified in protocol."}
• {"endpoint_text":"- Modified GIDS-PD","definition_or_measurement_approach":"Modified GIDS-PD score as defined in protocol; measured using the GIDS-PD instrument per protocol."}

Other endpoints

• {"endpoint_text":"- Reduction of faecal abundance of bacteria that produce levodopa-metabolizing enzymes after rifaximin treatment","definition_or_measurement_approach":"Measured by sequencing/quantification of faecal bacterial fragments (abundance) pre- and post-rifaximin treatment; comparison of abundance levels before and after treatment."}
• {"endpoint_text":"- Reduction of gastrointestinal symptoms after rifaximin treatment","definition_or_measurement_approach":"Measured by gastrointestinal symptom scores/questionnaires before and after rifaximin treatment; comparison of symptom scores pre- and post-treatment."}

Netherlands

Earliest CTIS Part Ii Submission Date

19-11-2024

Latest Decision Or Authorization Date

04-02-2026

Processing Time Days

442

Number Of Sites

1

Number Of Participants

81

Primary sponsor

Full Name

Stichting Radboud University Medical Center

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"EVER Neuro Pharma GmbH","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"MDL Fonds (Dutch Digestive Foundation)","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Stichting Woelse Waard","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"Stichting Alkemade-Keuls","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"ParkinsonNL","duties_or_roles":"Monetary support","organisation_type":""}